tbuckley/cabot-search huggingface dataset:
The role of immunotherapy in stage III large cell neuroendocrine carcinoma of the lung (LCNEC): A retrospective NCDB analysis.
Authors: Dawood Findakly, Runhua Shi, Kavitha Beedupalli
Journal: Journal of Clinical Oncology (2023)

e20568 Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer subtype. Despite advances in understanding lung cancer biology, a consensus on the use of consolidation immunotherapy (IO) in patients with LCNEC is still lacking. Methods: Using National Cancer Database (NCDB), we reviewed stage III lung LCNEC cases diagnosed from 2017 through 2019 with a follow-up through 2020. Several variables were incorporated into the multivariate logistic regression analysis, including age, gender, race, Charlson-Deyo comorbidity score (CDCS), insurance status, and IO use. Survival distribution was examined using the Kaplan-Meier analysis and compared by the log-rank test. Results: A total of 956 cases with a male:female ratio of 1.2:1, and a median age (±SD, range) of 66.4 (±9.7, 37–90) years—baseline characteristics are shown in the Table. In the univariate analysis, IO use (n = 184) resulted in a superior median overall survival (mOS; 30.6 vs. 20.3 months, HR 0.76, 95% CI 0.62-0.96, p = 0.02, compared to no IO use). Results from multivariate analysis further demonstrated survival benefit with IO use (HR 0.79, 95% CI 0.63-0.98, p = 0.03, compared to no IO use). Additionally, in the multivariate analysis, the female gender was associated with improved survival (HR 0.84, 95% CI 0.71-0.99, p = 0.04); while notable factors associated with reduced survival were age ≥75 years (HR 1.45, 95% CI 1.08-1.95, p = 0.01, compared to 18-64 years age group), CDCS of ≥1 (HR 1.19, 95% CI 1.004-1.420, p = 0.04, compared to zero), and Medicaid (HR 1.46, 95% CI 1.05-2.05, p = 0.02, compared to private insurance). There was no statistical significance for OS noted with age group 65-74 years (HR 1.09, 95% CI 0.84-1.42, p = 0.49, compared to 18-64 years age group); and race (African American, HR 1.001, 95% CI 0.77-1.29, P = 0.99, compared to White). Conclusions: This study shows that IO improves survival in stage III LCNEC. Despite the inherent limitations of the database, our findings are intriguing and warrant further evaluation through prospective clinical trials in order to assess and optimize the benefit of IO in this patient population. [Table: see text]
Camrelizumab combined with anlotinib and nab-paclitaxel in patients with untreated advanced mucosal melanoma: A single-arm, multicenter, exploratory study.
Authors: Di Wu
Journal: Journal of Clinical Oncology (2023)

TPS9593 Background: Anti-programed cell death-1 (PD-1) monotherapy is a part of the standard treatment for cutaneous melanoma, but its efficacy in mucosal melanoma is not ideal. In vivo studies have demonstrated that co-inhibition of the VEGF receptor (VEGFR) and PD-1 pathways increased T cell infiltration and suppressed tumor growth synergistically. Early phase trial data confirmed that PD-1 inhibitors combined with anti-angiogenic drugs showed efficacy in the treatment of advanced mucosal melanoma, but still did not meet clinical needs. Previous studies have shown that chemotherapy combined with anti-angiogenic drugs has significantly improved median PFS and median OS compared with chemotherapy alone, and has a certain effect as a salvage treatment for progression after PD-1 inhibitor treatment. In addition, previous retrospective analysis showed that PD-1 inhibitors combined with chemotherapy drugs such as nab-paclitaxel were superior to anti-PD-1 monotherapy in the treatment of advanced mucosal melanoma. In summary, the combination of anti-PD-1, anti-angiogenic drugs and chemotherapy may bring new hope for the treatment of advanced mucosal melanoma. Methods: This is a single-arm, multicenter, exploratory study to evaluate the efficacy and safety of camrelizumab combined with anlotinib and nab-paclitaxel as first-line therapy in patients with advanced mucosal melanoma. The trial is expected to enrol 66 patients. Key Inclusion Criteria are pts with confirmed recurrence, unresectable or metastatic mucosal melanoma after surgery (stage III/IV) and ECOG performance status of ≤1.Pts with previous adjuvant therapy or neoadjuvant therapy (except PD-1/PDL1 monoclonal antibody and VEGFR TKI) at least 4 weeks before the first administration of the study drug are allowed. Patients received intravenous camrelizumab (200 mg) on day 1, intravenous nab-paclitaxel (260mg/m 2 ) on day 1, and oral anlotinib (8mg) on days 1-14 every 3 weeks. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR),progression-free survival (PFS), and 2-year overall survival (OS). Clinical trial information: NCT04979585 .
The probability of lung cancer in patients with incidentally detected pulmonary nodules detected via low-dose computed tomography screening in China.
Authors: Guo Lan-Wei, Zhangyan Lyu, Shaokai Zhang
Journal: Journal of Clinical Oncology (2023)

10569 Background: Low dose computed tomography (LDCT) screening has been proven to be effective in reducing lung cancer mortality, but the ensuing high false-positive and overdiagnosis rates shackle the effectiveness of lung cancer screening (LCS) in China. Nodule malignancy prediction models may be an applicable solution. Methods: We developed and internally validated the model using data from the ongoing Henan province Cancer Screening Program in Urban China (CanSPUC). From 2013 to 2021, 23031 heavy smokers underwent baseline screening with LDCT; 2553 participants were diagnosed with pulmonary nodules. Detailed questionnaire, physical assessment and follow-up were completed for all participants. We then externally validated the model using the National Lung Screening Trial (NLST) dataset consisting of 10485 lung nodules in 4660 participants. Multivariable Cox proportional risk regression models were used. Data analysis was performed from July 1, 2022, through December 31, 2022. Results: A total of 111 and 1089 lung cancer cases with a median follow-up duration of 3.7 years occurred in the Henan CanSPUC and NLST study, respectively. Age, gender, physical activity, consumption of pickled food, history of silicosis or pneumoconiosis, nodule type, size, calcification, and pleural retraction sign were included into the model. The AUC (95% CI) of the model for 5-year lung cancer risk was 0.857 (0.801, 0.914) and 0.847 (0.829, 0.881) in the training set and validation set, respectively. Compared with Mayo model, VA model, PKU model, and Brock model, the Henan CanSPUC model yield statistically better discriminatory performance (all P values &lt; 0.05). The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups. Conclusions: The model developed and validated in this study may be used to estimate the probability of lung cancer in nodules detected at baseline LDCT, allowing more efficient risk-adapted follow-up in population-based LCS programs.
The association of race and curative-intent treatment with mortality outcomes among early-stage NSCLC.
Authors: Qinran Liu, Tulay Koru-Sengul, Gilberto Lopes, Paulo S. Pinheiro
Journal: Journal of Clinical Oncology (2023)

e20563 Background: Racial disparities in early-stage non-small cell lung cancer (NSCLC) survival have persisted between blacks and whites in the past few decades. The role of receipt of curative-intent surgery and/or stereotactic body radiation therapy (SBRT) in this disparity is unclear. We examined the associations of race/ethnicity and curative-intent treatment (surgery and/or SRBT) with mortality outcomes among early-stage NSCLC patients, using population-based data from Florida, the third largest state in the US and the second state in the number of cancer cases diagnosed annually. Methods: Florida Cancer Data System (FCDS) data were used to estimate cancer-specific mortality for all patients diagnosed in the state between 2007 to 2018 for each racial/ethnic group: non-Hispanic black (NHB), Hispanic, and Asian/Pacific Islander (API)) and non-Hispanic whites (NHW). FCDS were further individually linked to population-based discharge data (94% match rate) containing patient-level comorbidities and treatment-specific information. Multivariable Cox proportional hazards regression models were applied to study the association of race/ethnicity and curative-intent treatment with lung cancer-specific mortality (LCSM). Competing risk analysis (deaths by other causes) for LCSM was performed. Results: We identified 63,872 early-stage NSCLC patients; 83.2% NHW, 6.6% NHB, 8.7% Hispanic, 0.77% API, and 0.79% other races; 72.2% of patients received curative-intent treatment (surgery and/or SRBT). The median lung cancer-specific survival time for all patients was 5.43 years (95% CI, 5.30-5.56). After inclusion of all clinical and sociodemographic factors including stage at diagnosis and comorbidities, race/ethnicity (NHB vs NHW: hazard ratio [HR], 1.06; 95% CI, 1.00-1.11) and curative-intent treatment (SBRT vs curative-intent surgery: HR, 1.87; 95% CI, 1.78-1.97;) were both independently associated with LCSM. Nevertheless, after combining the effect of race/ethnicity and curative-intent treatment in the same fully adjusted model, NHB patients who received curative-intent treatment experienced nearly identical survival as their NHW counterparts (HR, 0.95; 95% CI, 0.87-1.03). Similar findings were observed in competing risk analysis (subdistribution hazard ratio [sHR], 0.97; 95% CI: 0.89-1.02). Conclusions: In this racially diverse population, receipt of curative-intent treatment revealed comparable survival between NHB and NHW patients. The results underscore the importance of considering receipt of (specifically) curative-intent treatment rather than receipt of any form of surgery or radiotherapy in racial/ethnic survival disparities. The uptake of curative-intent surgery and SBRT, which currently stands at 56.5% and 9.4% respectively, should be increased to improve survival outcomes for early-stage NSCLC for all.
Correlation of drug susceptibility testing on short term cultures of CTCs positively with clinical outcomes in non-small cell lung cancer.
Authors: Prashant Kumar, Sewanti Atul Limaye, Govind Babu Kanakasetty, Ajay Balakrishnan, Asim Joshi, Sindhu Govindan, R Venkataramanan, Moni Kuriakose
Journal: Journal of Clinical Oncology (2023)

e21177 Background: Enumeration of circulating tumor cells (CTCs) is rapidly emerging as a minimally invasive and reliable technique for monitoring disease progression and patient’s response to treatment. However, its utility beyond enumeration in clinical management of cancer remains scarcely explored. Being biologically similar to both primary and secondary tumors, CTCs may help in identification of most efficacious therapies. In this study, we propose a method for short term culture of CTCs thereby allowing to evaluate the drug susceptibility testing in individual patients. Methods: We obtained peripheral blood samples from 20 advanced stage lung cancer patients undergoing treatment at Kidwai Memorial Institute of Oncology, Bangalore, India. These blood samples were processed and cultured on ellipsoidal microwells maintained at hypoxic conditions (1% O 2 ). The CTC clusters were seeded onto 96 well plates coated with Matrigel and treated with the same drug regimen as the respective patients. The viability of the cells was measured using CellTitre-Glo. Results: Of the 20 samples, tight cluster formation was observed in four samples and drug susceptibility testing was performed. Based on clinical treatment received, we treated CTCs with combination of pemetrexed and carboplatin at respective Cmax concentrations of 5.68 and 3.68 µg/ml. The combination drug treatment resulted in decreased viability of CTCs to 30.7%. Notably, the CT scan images demonstrated significant reduction of pleural effusion in patient following treatment with carboplatin and pemetrexed, thus correlating with our in vitro drug susceptibility finding. Conclusions: In this proof of concept study, we demonstrate the feasibility of utilizing in vitro drug susceptibility testing on CTCs as an approach to guide patient specific chemotherapeutic treatment approaches, thus opening avenues for personalized treatments.
Interventions to improve outcomes for caregivers of patients with advanced cancer: A systematic review and meta-analysis.
Authors: Ronald Chow, Jean J Mathews, Emily YiQin Cheng, Samantha Lo, Joanne Wong, Sorayya Alam, Breffni Hannon, Gary Rodin, Rinat Nissim, Sarah Hales, Dio Kavalieratos, Kieran Quinn, George Tomlinson, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2023)

12026 Background: More than one in ten adults in the US are family caregivers, with cancer among the most common diagnoses of care recipients. Family caregivers of patients with advanced cancer often have poor quality of life (QOL) and mental health. We examined the effectiveness of interventions offering support for caregivers of patients with advanced cancer on caregiver QOL and mental health outcomes. Methods: We searched Ovid MEDLINE, EMBASE, Cochrane CENTRAL, and CINAHL databases from inception through 6/2021. Eligible studies reported on randomized controlled trials for adult caregivers of adult patients with advanced cancer. Meta-analysis was conducted for primary outcomes of QOL, physical well-being, mental well-being, anxiety, and depression, from baseline to follow-up of 1-3 months; secondary endpoints were these outcomes at 4-6 months and additional caregiver burden, self-efficacy, family functioning and bereavement outcomes. Random effects models were used to generate summary standardized mean differences (SMD). Meta-regression was conducted for primary outcomes that were significant for the intervention, assessing for mediation effect modification by caregiver sex and age of patient and caregiver. Type I error was 0.05. PROSPERO Registration: CRD42019136321. Results: Of 12,193 references identified, 56 articles reporting on 49 trials involving 8,554 caregivers were eligible for analysis; 16 (33%) targeted caregivers (mostly psychoeducational or problem-solving interventions), 19 (39%) patient-caregiver dyads (mostly counseling/therapy), and 14 (29%) patients and their families (mostly palliative care teams). At 1-3 month follow-up, interventions had a significant effect on overall QOL (SMD 0.24 (0.10 to 0.39), I2 = 52.0%), mental well-being (SMD 0.14 (0.02 to 0.25), I2 = 0.0%), anxiety (SMD 0.27 (0.06 to 0.49), I2 = 74.0%), and depression (SMD 0.34 (0.16 to 0.52), I2 = 64.4%), compared to standard care. At 1-3-month follow-up, a larger age difference (older patient and younger caregiver) was associated with a greater positive effect on QOL (p = 0.04) and depression (p = 0.02). In narrative synthesis, interventions demonstrated improvements in caregiver self-efficacy and grief. Conclusions: Interventions targeting caregivers, dyads, or patients and families led to improvements in caregiver QOL and mental health outcomes. These data support the routine provision of available interventions to support caregivers of patients with advanced cancer.
Management of patients with <i>ALK</i>-positive advanced non-small cell lung cancer who received brain radiotherapy on study in the phase 3 CROWN trial.
Authors: Todd Michael Bauer, Enriqueta Felip, Tony S. K. Mok, Yi-Long Wu, Geoffrey Liu, Yasushi Goto, Dong-Wan Kim, Jolanda Paolini, Anna Polli, Benjamin J. Solomon
Journal: Journal of Clinical Oncology (2023)

9063 Background: Approximately 30% of patients with ALK-positive non-small cell lung cancer (NSCLC) present with brain metastases at diagnosis. Lorlatinib is a potent brain-penetrant ALK tyrosine kinase inhibitor (TKI) that showed improved time to intracranial (IC) progression compared with crizotinib in patients with and without brain metastases at baseline. This post hoc analysis from the phase 3 CROWN study summarizes the management of patients who received brain radiotherapy (RT) during the study. Methods: In the CROWN study, 296 patients with previously untreated ALK-positive advanced NSCLC were randomized 1:1 to receive oral lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). Patients who received brain RT while on study treatment or after the initiation of subsequent systemic anticancer therapy were included in this post hoc analysis. Results: As of September 20, 2021, at approximately 3 years of follow-up, median time to IC progression was not reached (NR; 95% CI, NR-NR) in the lorlatinib arm and was 16.6 (95% CI, 11.1-NR) months in the crizotinib arm. At the time of this analysis, 4 of 149 patients (2.7%) in the lorlatinib arm and 20 of 147 patients (13.6%) in the crizotinib arm received brain RT; study treatment was ongoing in 2 of 4 patients (50.0%) in the lorlatinib arm and discontinued in all 20 patients in the crizotinib arm. Median time from randomization to first brain RT was 18.2 (range, 6.4-31.3) months in the lorlatinib arm and 11.1 (range, 2.5-37.5) months in the crizotinib arm. In patients who had brain RT, median duration of treatment was 20.0 (IQR, 6.3-37.1) months with lorlatinib and 7.8 (IQR, 4.0-11.1) months with crizotinib. In the lorlatinib arm, 2 of 4 patients (50.0%) received concomitant brain RT and continued lorlatinib beyond progression. In the crizotinib arm, patients received brain RT while on study treatment or on subsequent systemic anticancer therapies with ALK TKIs or chemotherapy. Follow-up analysis is ongoing. Conclusions: At approximately 3 years of follow-up in the CROWN study, fewer patients in the lorlatinib arm received brain RT than those in the crizotinib arm. At the time of this analysis, study treatment was ongoing in 2 of 4 patients (50.0%) in the lorlatinib arm but was discontinued in all patients in the crizotinib arm. Patients were mostly managed with other ALK TKIs and/or chemotherapy following brain RT in the crizotinib arm. ClinicalTrials.gov: NCT03052608. Clinical trial information: NCT03052608 .
Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy: A single-arm phase II trial.
Authors: Huaying Wang, Wenjuan Tian, Yulan Ren, Jing Lu, Tingting Wang, Haiming Li, Chuyu Jing, Boer Shan, Huijuan Yang, Xi Cheng
Journal: Journal of Clinical Oncology (2023)

5516 Background: The first stage results of a Simon’s two-stage single-arm phase II trial showed promising antitumor activity and manageable safety of camrelizumab (a humanized anti-PD-1 monoclonal antibody) plus apatinib (a highly selective VEGFR2 inhibitor) in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy. Here, we report the primary results of this trial. Methods: This open-label, single-arm, phase II trial used a minimax Simon’s two-stage design. Patients with advanced or recurrent endometrial cancer that had progressed after at least one prior systemic therapy were treated with camrelizumab (200 mg, intravenously, every two weeks) and apatinib (250 mg, orally, daily) on a four-week cycle until disease progression or intolerable toxicity. The primary endpoint was the objective response rate per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other assessed endpoints were disease control rate, time to response, duration of response, time to treatment failure, progression-free survival, overall survival, and treatment-related adverse events. Results: Between January 20, 2020 and October 14, 2022, 36 patients (median age: 60 [range: 29, 76] years; 17 [47.2%] had Eastern Cooperative Oncology Group [ECOG] performance status 1; 15 [41.7%] had received at least two prior systemic therapies) were enrolled. At the date of data cutoff (December 31, 2022), the median follow-up time was 13.9 (interquartile range: 5.8-23.2) months. All 36 patients were evaluable for efficacy, the confirmed objective response rate was 44.4% (95% CI: 27.9%, 61.9%) and the conformed disease control rate was 88.9% (95% CI: 73.9%, 96.9%), with two complete response, 14 partial response, and 16 stable disease. The median progression-free survival was 6.4 (95% CI: 5.2, 13.0) months. The treatment-related adverse events of grade 3 or greater occurred in 19 (52.8%) patients, with increased gamma-glutamyltransferase (8 [22.2%]), hyperglycemia (4 [11.1%]), hypertension (4 [11.1%]) and increased direct bilirubin (4 [11.1%]) being most common. Reactive cutaneous capillary endothelial proliferation occurred in 6 (16.7%) patients and all were grade 1 or 2. No treatment-related death occurred. Conclusions: Camrelizumab plus apatinib show promising antitumor activity and manageable toxicity in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy and warrant further investigation. Clinical trial information: ChiCTR2000031932 .
Circulating tumor DNA–based detection of molecular residual disease as a biomarker for recurrence monitoring predict disease recurrence in patients with ovarian cancer.
Authors: Tianjiao Lv, Xinyi Shi, Dan Zhao, Jing Sun, Bo Wang, Kai Lu, ShiPing Zou, Jing Wang, Qiang Wang, Weiwei Feng
Journal: Journal of Clinical Oncology (2023)

e17542 Background: Despite recent advances in cancer diagnostics and treatments, nearly 75% ovarian cancer patients relapse within two years of primary therapy and become candidates for treatment of recurrent diseases. A novel approach to post-surgical risk stratification for molecular residual disease (MRD) detection and treatment monitoring is needed to improve patient outcomes. Methods: We analyzed a cohort of 22 stage Ⅰ-Ⅳ ovarian cancer patients which were followed up at median 6 (range,3-15) times between July 2017 and December 2020. Among the 22 patients, stage I, II, III and Ⅳ comprised 9%, 5%, 50% and 36%, respectively. Tumor tissue and blood samples of all subjects were collected at Ruijin Hospital, Shanghai Jiao Tong University.Somatic mutations were identified by whole exome sequencing and assessed from plasma collected during treatment using personalized tumor-informed MRDtect assays with a median of 25（range,17-30） amplicons/assay targeting tumor-specific variants unique to each patient, sequenced at mean 200,000X depth. Plasma samples with ≥2 variants detected were considered MRD-positive and ctDNA levels were reported in mean tumor molecules per mL (MTM/mL) of plasma. Sequencing data were analyzed using PiVAT secondary analysis software and MRD positive was concluded when at least two variants were detected in plasma. Results: CtDNA was preoperatively detectable in 18 (85.7%) patients, and the positive rate became 38.8% (7/18) after surgery. Serial ctDNA analysis during surveillance after definitive treatment of the 22 patients with longitudinal collected plasma samples identified relapse with 100% sensitivity and 100% specificity. The median lead time from ctDNA detection in plasma to relapse detection by standard-of-care computed tomography was 135 days (range,45-387days). Variants from a total of 526 genes were selected from the WES results of these 22 patients. Among these 526 genes, 96% (505 genes) were selected for only one patient, 3.4% (18 genes) were selected for two patients and 0.2% (one gene) were selected for three patients. Compared with tumor-agnostic assay, tumor-informed assay is a more accurate route that is more consistent with the heterogeneity of tumor and can maximize the ability to reflect the real situation of each patient. Conclusions: Sensitive methods for risk stratification, therapeutic efficacy monitoring, and early relapse detection may have a major impact on treatment decisions and patient management for ovarian cancer patients. MRD can be used as an effective biomarker to prompt prognosis and recurrence risk, providing powerful assistance for accurate diagnosis and treatment for patients.